Single Living Cell Analysis Nanoplatform for High-Throughput Interrogation of Gene Mutation and Cellular Behavior.
Zaizai DongShi YanBing LiuYongcun HaoLong LinTianrui ChangHong SunYusen WangHu LiHan WuXinxin HangShiqi HeJiaming HuXinying XueNan WuLingqian ChangPublished in: Nano letters (2021)
The genetic heterogeneities in cancer cells pose challenges to achieving precise drug treatment in a widely applicable manner. Most single-cell gene analysis methods rely on cell lysis for gene extraction and identification, showing limited capacity to provide the correlation of genetic properties and real-time cellular behaviors. Here, we report a single living cell analysis nanoplatform that enables interrogating gene properties and drug resistance in millions of single cells. We designed a Domino-probe to identify intracellular target RNAs while releasing 10-fold amplified fluorescence signals. An on-chip addressable microwell-nanopore array was developed for enhanced electro-delivery of the Domino-probe and in situ observation of cell behaviors. The proof-of-concept of the system was validated in primary lung cancer cell samples, revealing the positive-correlation of the ratio of EGFR mutant cells with their drug susceptibilities. This platform provides a high-throughput yet precise tool for exploring the relationship between intracellular genes and cell behaviors at the single-cell level.
Keyphrases
- single cell
- high throughput
- rna seq
- genome wide
- copy number
- cell therapy
- induced apoptosis
- small cell lung cancer
- photodynamic therapy
- stem cells
- cell proliferation
- cell cycle arrest
- quantum dots
- signaling pathway
- endoplasmic reticulum stress
- tyrosine kinase
- drug delivery
- cell death
- mass spectrometry
- drug induced
- high speed